Hematopoietic stem cells (HSCs) are a rare and essential population responsible for maintaining lifelong blood cell production. Their ability to self-renew and differentiate is crucial for sustaining a healthy blood and immune system. However, disruptions in these regulatory processes can result in hematological disorders, including leukemia. Understanding the molecular mechanisms that govern HSC identity and function is fundamental to uncovering how such dysregulations contribute to disease development.
Long non-coding RNAs (lncRNAs) have emerged as key regulators of gene expression, yet their roles in HSC biology and leukemia remain largely unexplored. Unlike protein-coding RNAs, lncRNAs function as regulatory molecules, influencing gene activity and cellular behavior. Recent evidence suggests that lncRNAs play a crucial role in stem cell function, making them promising candidates for understanding hematopoiesis and developing novel therapeutic approaches for leukemia and other blood disorders.
The StemLinc project, funded by the Marie Skłodowska-Curie Actions (MSCA) program, aimed to identify and characterize lncRNAs involved in the regulation of HSC stemness and their potential role in leukemia.
The project’s specific objectives were:
To generate a comprehensive catalog of hematopoietic lncRNAs through deep total RNA sequencing of primary mouse blood cells and bioinformatics analysis.
To infer the function of identified lncRNAs using computational approaches integrating genomic, epigenomic and transcriptomic data.
To validate the role of selected candidate lncRNAs through functional experiments and assess their relevance in leukemia.
By integrating advanced transcriptomics, functional genomics, and computational analyses, StemLinc significantly advances multiple scientific domains:
Hematopoietic system biology: Providing new insights into the transcriptional landscape of HSCs, progenitors, and differentiated blood cells.
ncRNA biology: Characterizing previously unexplored lncRNAs, including mono-exonic transcripts, broadening the understanding of non-coding RNA regulation in hematopoiesis.
Resource development for future research: Identifying candidate lncRNAs strongly associated with HSC identity and function, offering valuable insights for disease biomarker discovery and future large-scale studies.
